Be Wary of the Magical, Hyped-Up Claims About DNA

We should be wary of accepting bold claims by researchers until they have been thoroughly tested.

It seems like every other week brings exciting news in the field of genetics.

After a closed-door meeting organized by Harvard University biologist George Church, rumor mills were buzzing about a plan to create a fully synthetic human genome. Church confirmed those rumors and several weeks later, the group published a proposal in Science. Their ten-year, $100 million proposal, dubbed the Human Genome Project-Write (HGP-Write), will use genetic engineering and synthetic biology to manufacture a human genome in the lab. Its goal is eventually reducing the cost of reading and writing the human genome.

Much like the original human genome project (HGP-Read), the HGP-Write proposal makes grandiose claims of how this technology could solve problems ranging from organ donation, viral immunity, vaccines, and cancer to testing new pharmaceuticals.

The HGP-Write project is one of several genetic-based technologies in the spotlight. The new gene editing powertool, CRISPR-Cas9, has made headlines for its ability to edit DNA in a cut-and-paste fashion. Last year, scientists from China used this technology to edit the genes that cause β-thalassaemia in a non-viable human embryo. While the US has sustained a moratorium on editing human embryos and the UK permits it with qualification, the number of published papers using CRISPR-Cas9 has increased substantially in the last couple of years.

Other genetics headlines include so-called “three-parent IVF.” Researchers from the UK sought approval to work on an IVF technique in which an embryo would be made from three genetic parents, ostensibly to remove faulty mitochondrial DNA from the mother’s egg while leaving her nuclear DNA intact.

And, finally, genetic testing has made headlines as both a diagnostic tool and, more controversially, as a way to predict a person’s future risk for certain diseases. Tests for the genes BRCA1 and BRCA2 increased when Hollywood star Angelina Jolie wrote about her double mastectomy. The genetic testing company 23andMe made headlines when it was under scrutiny by the U.S. Food and Drug Administration, although that agency eventually approved direct-to-consumer genetic testing with limitations. For many people genetic tests have provided answers about rare genetic-based diseases. For others, it has led to distress.

Genetics has explanatory power. Genetic mutations can explain the basis of hereditary diseases and the causes of cancer. However, the rhetoric doesn’t end with evidence-based explanations.

A genetics narrative is also being invoked to explain the big questions of life. Genetics is used to explain why one person suffers from cancer while someone else does not. Or why a young man is an alcoholic like his father or why a woman struggles with depression. Genetics has been invoked to explain violence and mass murders. In other words, for many, genetics is being used to answer the big questions of life: Where did we come from (both our ancestry and human origins)? Where do evil and suffering come from? How can we fix our broken humanity?

For many scientists, particularly those viewing all of life’s ills through the lens of genetics, truth is found by reducing an organism to its component parts, to its chemistry.

But what of the mistakes and anomalies? Have we really found the essence of life, as Nobel laureate James Watson puts it, by studying its parts? The genetics narrative may not be as air-tight as it is made out to be.

Direct-to-Consumer Tests

Where genetic testing has proved most helpful is in identifying genetic diseases. Research on rare diseases has flourished with the help of genetic testing and sharing genetic data. This has provided families with much-needed answers and researchers with therapeutic targets.

However, genetic tests, particularly direct-to-consumer tests, have their flaws. Journalist Kira Peikoff made headlines in 2013 when she ordered genetic tests from three well-known companies and received contradictory results. Since then the FDA has demanded more rigorous standards.

Direct-to-consumer tests do not sequence your entire genome, but only small segments of DNA that house known mutations for diseases, making them less reliable. But this is often lost on consumers who take markers for complex diseases, such as Type I diabetes, as definitive.

Even though the results of direct-to-consumer testing are not necessarily deterministic, insurance companies still take the results into account. In the US genetic discrimination laws prohibit health insurance companies from discriminating based on genetics, but they do not prevent other types of insurance companies, such as life and disability, from taking direct-to-consumer tests into account and in some cases denying coverage completely.

Genetic Superheroes

Where genetic tests have been most helpful is in detecting diseases caused by single genes. There are some diseases that are “fully penetrant,” meaning that if you have the mutation, you will eventually get the disease. Huntington’s disease, which affects muscle coordination and causes mental decline, is one of the best-known of these. However, even in the case of fully penetrant diseases, there are still exceptions. Earlier this year a study investigated why certain people who have genes for fully penetrant diseases do not show any signs of the disease, so-called “genetic superheroes.” Researchers looked for what was blocking these genes from being expressed. Their results were inconclusive.

Forensics

Television crime dramas are today’s version of the mystery novel. Nowadays the formula for solving the crime isn’t matching fingerprints but collecting DNA left at the crime scene. However, in real life, DNA matching is not nearly so definitive.

According to The Atlantic, forensics can be an interpretive art rather than exact science particularly in samples containing several people’s DNA. Two different forensics experts may come up with two different answers as to whether the DNA is a match to a suspect. Unfortunately, this ambiguity is lost on juries who believe DNA evidence is as airtight as it is on television.

Then there is the problem of the technique being too sensitive to the point that much is made over very little evidence. One example mentioned by The Atlantic was the case of Lukis Anderson, a homeless man in California with a history of non-violent crimes. He was implicated in the murder of a millionaire at his mansion because some of Anderson’s DNA was found under the millionaire’s fingernail. It turns out that Anderson had been taken to the hospital earlier that day by the same paramedics who picked up the millionaire. The same oxygen monitor had been used on the fingers of Anderson and the victim.

Epigenetics

Epigenetics is a newer field that studies how environmental factors affect the way the genome is read. A key idea is that the genome is more than a sequence of letters that code for proteins. The three-dimensional position of those letters with respect to each other, as well as chemical modifications to DNA nucleotides, plays a role in which genes are turned on or off. Those chemical modifications may be inherited or they may be due to environmental factors. In some cases, it may be both.

The role of epigenetics in mental health is a particularly controversial topic. Research indicates that epigenetics, as well as other factors, play some role in the genetic component of mental illness, but the specifics are still poorly understood. Mental illness is particularly complex, causing researchers to question how meaningful genetic tests really are.

In an article critical of the use of genetic testing for mental illness, Dr Steve Dobovsky points out that genetic associations are statistical while medical practice is personal, “Yet there is tremendous pressure to translate each new report of such associations to our patients, not only from our own need to appear ‘scientific’ and from industry marketing of proprietary tests, but from the marketing of ideas by thought leaders with an intellectual attachment to the latest conceptualization of genetic causality.”

Why Write the Genome?

One of the objections to the HGP-Write proposal is the possibility of making a human being who would not have genetic parents. While this is an interesting ethical question, probably the more pressing question is whether the impetus behind this expensive project is based on actual scientific evidence or reductionist assumptions. A strong commitment to reductionism leads to faith in a narrative that may be existentially compelling but scientifically problematic. As the American journalist H.L. Mencken once wrote long ago, “there is always a well-known solution to every human problem — neat, plausible, and wrong.”

This piece originally appeared at Mercatornet, and is reprinted with that site’s kind permission.

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m-nj

good common sense assessment of the hype. as someone who actually does DNA manipulation for microbial biotechnology uses, it is a lot more complicated and difficult than most news articles convey (and that is for very simple bacteria, let alone very complex human beings).

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